TOP 5 h CLINICAL PATHOLOGY h PEER REVIEWED

Top 5
Breed-Associated
Biochemical
Abnormalities
Julie Allen, BVMS, MS, MRCVS, DACVIM
(SAIM), DACVP (Clinical)
Durham, North Carolina

The serum chemistry profile is a primary com- Following are the author’s top 5 breed-specific biochem-
ical abnormalities.
ponent of the minimum database. However,

test results should always be interpreted in
relation to other patient findings including
signalment, history, and physical examination
findings.
Of particular importance is the patient’s breed, which
should always be considered when interpreting results.
Because breed-specific reference intervals are not estab-
lished for every breed, it is important to be aware of
parameters that may lie outside reference intervals but
may be frequently encountered without obvious pathol-
ogy in a particular breed. Conversely, it is also impera-
tive to know when an abnormal laboratory result is of
concern for a certain breed due to an associated disease
predisposition.
1
Increased ALP in Scottish Terriers
Some studies have documented persistent,
progressive increases in ALP levels in Scottish
terriers1-3 resulting from increased synthesis
TOP 5 BREED-ASSOCIATED
BIOCHEMICAL ABNORMALITIES
1. Increased ALP in Scottish terriers
2. Increased BUN in Yorkshire terriers
3. Increased creatinine in greyhounds
4. Increased ALT in Labrador retrievers
5. Increased lipase in boxers

January/February 2021 cliniciansbrief.com 21

TOP 5 h CLINICAL PATHOLOGY h PEER REVIEWED
and release from biliary epithelium, hepatocytes,
or bone.4 Induction can be stimulated by cholesta-
sis, certain drugs (eg, corticosteroids), and hor-
mones, as well as increased osteoblastic activity.
The corticosteroid-induced isoform is most often
increased in this breed.1,3
Increased ALP levels typically occur in the absence
of notable clinical signs, although some clinicians
have suggested that some neutered male dogs
develop prostatomegaly and some Scottish terriers
may display polyuria/polydipsia. However, few of
these dogs test positive for hyperadrenocorticism
on routine screening (eg, low-dose dexamethasone
suppression), whereas others have increased levels
of sex steroid hormones (predominantly proges-
terone and androstenedione).1,3 In a study of dogs
that tested positive for hyperadrenocorticism and
were treated with trilostane, treatment was inef-
fective in all the dogs and detrimental in some
cases, possibly due to the increases in sex steroid
hormones.2 Of note, clinically normal dogs should
not be tested for hyperadrenocorticism.
A genetic defect similar to the 21-hydroxylase defi-
ciency that causes adrenal hyperplasia in humans​
is suspected to be the cause of increased ALP levels
in Scottish terriers.1,3 The disorder causes no clini-
cal abnormalities in some dogs, whereas others
gradually develop a degenerative vacuolar hepa-
topathy that occasionally progresses to hepatic
insufficiency, sometimes with secondary portal
hypertension.2 Increased hepatic copper levels may
also occur, and some dogs develop hepatocellular
Increased ALP in Scottish
terriers should not be
dismissed as inconsequential
and warrants continued
monitoring and additional
diagnostics as needed.
22 cliniciansbrief.com January/February 2021
carcinoma​.2 As a result, increased ALP in Scottish
terriers should not be dismissed as inconsequential
and warrants continued monitoring and additional
diagnostics (eg, abdominal ultrasonography, bile
acids) as needed.
2
Increased BUN in Yorkshire Terriers
Yorkshire terriers anecdotally have a
higher incidence of increased BUN as
compared with other breeds. However,
this abnormality is often associated with normal
creatinine levels and adequately concentrated
urine, suggesting a prerenal cause. Differential
diagnoses for prerenal causes of increased BUN in
dogs include dehydration, GI bleeding, consump-
tion of a high-protein diet, and increased protein
catabolism (eg, due to strenuous exercise or corti-
costeroids), but in a large percentage of Yorkshire
terriers, these causes are excluded.5
Yorkshire terriers are predisposed to GI disease,
including protein-losing enteropathies (eg,
lymphangiectasia).6 Thus, it has been postulated
that the increased BUN may result from subclini-
cal GI bleeding, although these patients do not
appear to develop signs of iron-deficiency anemia
and anecdotally have no response to GI-protectant
therapy. In addition, a recent study in Yorkshire
terriers with protein-losing enteropathy identified
low BUN among the clinical pathologic findings.7
To further confound the issue, this breed has an
increased incidence of congenital liver disease and
corresponding decreased BUN synthesis.6
A renal origin cannot be completely excluded,
however, as some Yorkshire terriers have concur-
rent proteinuria and, in one study, this breed
accounted for 5.8% of biopsy-confirmed cases of
immune-mediated glomerulonephritis,8 perhaps
supporting glomerulotubular imbalance (anec-
dotal). Consequently, a cause for the increase
remains unclear and more research (eg, evaluating
SDMA) is needed. In the interim, high-protein
diets, GI bleeding, and renal dysfunction should
be eliminated as potential causes of increased
BUN. Anecdotally, the biochemical abnormality
does not appear to have much impact clinically in
Yorkshire terriers.
3
Increased Creatinine in Greyhounds
Greyhounds are considered an idiosyn-
cratic breed due to several clinical pathol-
ogy variables that often fall outside
standard reference intervals.9 One of the best-
described is increased creatinine levels (mean,
1.6 mg/dL vs 1.0 mg/dL).9 Creatine is synthesized
in the liver from glycine and arginine, after which
it is transported to muscle (skeletal and cardiac)
and phosphorylated to phosphocreatine in a reac-
tion catalyzed by creatine kinase. Phosphocreatine
then acts as the major energy store for muscle by
donating phosphate during episodes of decreased
adenosine triphosphate (ATP). The residual cre-
atine is then degraded to creatinine, which is
excreted essentially unchanged from the kidneys.5
Various causes have been proposed for the
increased creatinine levels in greyhounds, includ-
ing decreased glomerular filtration rates, although
this was not substantiated.9 Eating a high-meat
diet (eg, one typically fed to racing dogs) has also
been suggested as a factor; however, in one study,
elevations persisted after dogs were retired and
fed a more conventional diet.10 The increase has
also been anecdotally attributed to higher body
stores of phosphocreatine as a result of increased
muscle mass, which could also account for the
higher ALT levels seen in this breed.9 Conse-
quently, mild increases in creatinine levels (up to
2.1 mg/dL) in clinically normal greyhounds may
not require further diagnostic investigation.9
Mean SDMA level is also higher in greyhounds
than in other dogs and has a different reference
interval.11 However, this biomarker is believed to
be unaffected by lean muscle mass, so further
research into the exact cause of increased creati-
nine in this breed is warranted.
4 Increased ALT in Labrador Retrievers
Labrador retrievers are predisposed to
chronic hepatitis due to excessive copper
accumulation12-14; idiopathic chronic
hepatitis has also been noted. Labrador retrievers
with this disorder may be subclinical or have signs
that range from mild and nonspecific to indicators
of severe liver disease, such as jaundice or ascites.
The copper-associated form of the disease appears
to have both genetic (ie, ATP7A and ATP7B gene
mutations) and dietary (ie, increased levels in
commercial dog food) causes.15,16 Liver biopsy with
histopathology is required for definitive diagnosis
(and ideally for monitoring). Mononuclear or
mixed inflammatory infiltrates with hepatocyte
necrosis and/or apoptosis and varying degrees of
fibrosis are found on biopsy. Histochemical stain-
ing and quantification of hepatic copper levels are
also essential.13
ALT is a moderately specific indicator of hepatocel-
lular injury in dogs, and an increase in ALT levels is
the most common clinicopathologic abnormality
noted in Labrador retrievers with chronic hepati-
tis.4,17 Although ALT measurement is an acceptable
predictor of histopathologic evidence of chronic
hepatitis, its sensitivity is poor in the earlier
stages of disease.17 As a result, it has been sug-
gested that a different reference interval with a
lower upper limit be considered for this at-risk
breed. Circulating microRNAs and testing for
ATP7A and ATP7B gene mutations for diagnosis
and, in the case of microRNAs, monitoring the
disease may also be valuable.15,18 Doberman pin-
schers, American and English cocker spaniels,
An increase in ALT levels
is the most common
clinicopathologic
abnormality noted clinically
in Labrador retrievers with
chronic hepatitis.4,17
ATP = adenosine triphosphate
January/February 2021 cliniciansbrief.com 23
TOP 5 h CLINICAL PATHOLOGY h PEER REVIEWED
West Highland white terriers, English springer
spaniels, and Bedlington terriers are also predis-
posed to chronic hepatitis. Increased ALT in any of
these breeds should not be overlooked. Persistent
ALT increases should be evaluated further with
bile acids and abdominal ultrasonography,
although hepatic biopsy with histopathology and
copper quantification is ultimately required for
definitive diagnosis.
5
Increased Lipase in Boxers
Hyperlipasemia has been noted in boxers.
Lipase has several sources but is usually
of pancreatic origin.4 Some assays (eg,
the 1,2-o-dilauryl-rac-glycero-3-glutaric acid-
[6’-methylresorufin] ester [DGGR] lipase assay)
are considered to be more specific for the pancre-
atic isoenzyme than others.19 In general, lipase
can be increased with pancreatitis, GI disease,
exogenous steroids, decreased glomerular filtra-
tion rate (lipase is renally excreted), and, rarely,
hepatic or pancreatic neoplasia.4 Boxers with
hyperlipasemia are often clinically normal and
have no GI signs or other manifestations (includ-
ing laboratory abnormalities) consistent with pan-
creatitis (anecdotal). This has led to speculation
that boxers may have higher values as a “normal”
finding and may warrant a breed-specific reference
Increased lipase levels
may be less of a concern
in boxers than in other
breeds, particularly in
the absence of clinical
signs.
24 cliniciansbrief.com January/February 2021
interval.20 However, in a postmortem study, pan-
creatitis was reported with a higher incidence in
boxers than in other breeds,21 although only 2 of
the 200 cadavers examined were boxers. The breed
disposition for this disorder was suggested again
in a study in which 4 of 61 dogs with chronic pan-
creatitis were boxers.22 If boxers are predisposed
to pancreatitis, it seems to be subclinical in most
cases. An increased prevalence of chronic pancre-
atitis may eventually result in exocrine pancreatic
insufficiency; however, another study found that
boxers are in fact at lower risk for pancreatic
insufficiency than are other breeds.23
Boxers are at extremely low risk for diabetes melli-
tus but at higher risk for insulinoma.24 The genetic
reasons for these findings remain unknown, but
an abstract several years ago noted that islet cells
in boxers were larger than those in other breeds,
suggesting higher β-cell mass due to increased
islet regeneration and/or reduced apoptosis.25 The
larger islet cells could explain this breed’s resis-
tance to diabetes mellitus and predisposition to
insulinoma. Perhaps the exocrine pancreas in
boxers also has greater mass compared with other
breeds, which may account for the hyperlipasemia.
More research is needed into the pancreata of this
breed, but it is possible that increased lipase levels
may be less of a concern in boxers than in other
breeds, particularly in the absence of clinical
signs.
Conclusion
It is important to recognize that these abnormali-
ties may represent underlying pathologic or, in
some cases, subclinical disease processes, versus
an expected or “normal” finding in a specific
breed. These biochemical abnormalities also pro-
vide another rationale for serial monitoring of lab-
oratory test results to assess persistence and/or
progression. n
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